Although increase in size and number of mitochondria in skeleletal muscle is a well-known adaptation to endurance exercise, mechanisms for exercise-induced mitochondrial biogenesis remain unclear. Nuclear respiratory factor I (NRF-I) has been identified as an early-responding protein after exercise and has been suggested to coordinate transcription of mitochondrial enzymes. The goal of the proposed research is to examine potential pathways for exercise-induced mitochondrial biogenesis. First, a single bout of exercise known to increase expression of mitochondrial enzymes in rats will be used to determine the time course of NRF-1 expression. Second, possible exercise-related mechanisms for an increase in mitochondrial proteins, including increased intracellular cAMP, increased Ca2+, and reduced phosphorylation potential will be examined using cell culture models.